Increased expression of extracellular matrix regulators TIMP1 and MMP1 in deteriorating heart failure

Paul J.R. Barton, Emma J. Birks, Leanne E. Felkin, Martin E. Cullen, Maren U. Koban, Magdi H. Yacoub

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Background: The authors previously identified and compared alterations in gene expression in the myocardia of patients with deteriorating heart failure who underwent left ventricular assist device (LVAD) implantation with those of patients with stable end-stage failure (ESF). We hypothesized that matrix metalloproteinases (MMPs) and their endogenous inhibitors, the tissue inhibitors of MMPs (TIMPs), would be implicated in the mechanisms that underlie deteriorating heart failure. Methods: Gridded macro-array filters were used to provide a broad overview of MMP and TIMP mRNA expression in heart failure. Precise mRNA levels of TIMP1, MMP1, and β-spectrin were determined using quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) of myocardial samples from 27 patients with deteriorating heart failure who underwent LVAD implantation, from 17 patients with stable ESF who underwent elective heart transplantation, and from 28 donor organs with good hemodynamic function. Results: Gridded macro-arrays analysis of pooled failing heart samples determined that TIMP1 mRNA was the most readily detectable TIMP in failing myocardium. Quantitative RT-PCR showed that expression levels in individual patients were similar in patients with stable ESF (1.00 ± 0.24, n = 17) and in donor organ samples (1.49 ± 0.22, n = 28) but were significantly increased in the deteriorating heart failure group (5.38 ± 0.32, n = 26, p < 0.0001 compared with patients with ESF). Similarly, MMP1 levels did not differ between donor and ESF groups but increased in the deteriorating failure group (6.04 ± 0.50, n = 27, p < 0.001 compared with the ESF group). Levels of β-II spectrin were the same in all 3 groups. Both TIMP1 and MMP1 showed positive correlation with each other and with previously determined levels of mRNA for both interleukin-1β (IL-1β) and IL-6 in this patient series when considering all patients individually, but neither correlated with tumor necrosis factor α. Conclusions: Patients with deteriorating heart failure have increased expression of TIMP1 and MMP1 mRNA. Correlation with pro-inflammatory cytokines suggests common pathways of regulation and potential activation by IL-6 and IL1-β.

Original languageEnglish
Pages (from-to)738-744
Number of pages7
JournalJournal of Heart and Lung Transplantation
Issue number7
StatePublished - Jul 1 2003

Bibliographical note

Funding Information:
This work was supported by the British Heart Foundation (Chair support to MHY and Senior Research Fellowship support to PJRB) and by the Harefield Research Foundation.

Copyright 2008 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation


Dive into the research topics of 'Increased expression of extracellular matrix regulators TIMP1 and MMP1 in deteriorating heart failure'. Together they form a unique fingerprint.

Cite this